Malaria is a protozoan infection widely distributed in tropical to subtropical regions. About 80% of the patients with malaria is infected with Plasmodium falciparum, a Plasmodium species parasitic on humans, and this is a very dangerous infection causing death in serious cases. Furthermore, due to recent global warming, malaria is not only endemic in developing countries in tropical and subtropical regions but also seems to be spreading in developed countries in temperate regions.
For Plasmodium species parasitic on humans, chloroquine and fansidar (a drug combination of pyrimethamine and sulfadoxin), which are called a traditional drug and were developed in the 1930s to the 1960s, have been used. Later, artemisinin derivatives, an active ingredient of Artemisia annua, a herbal drug, was developed after the 1980s, and have been used.
However, Plasmodium resistant to chloroquine and/or fansidar and Plasmodium resistant to a multidrug containing those have emerged. There is also a report on the emergence of protozoa resistant even to artemisinin derivatives which was developed later.
In response to the emergence of such protozoa resistant to existing drugs, antimalarials effective for Plasmodium species have been developed worldwide. However, in the development of antimalarials, in many cases the antimalarial activity identified in vitro cannot be identified in vivo, or drugs are found to be toxic, and thus few drugs have been found to be effective for drug-resistant strains and have antimalarial activity in vivo.
Heretofore 2,4,5-substituted pyrimidine derivatives (Non patent document 1 and Patent document 1) and 2,4,6-substituted pyrimidine derivatives (Non patent document 2) have been reported as a substance having antimalarial activity, but no compounds are known to have the structure of the compound of the present invention.